Vessel for reduction of extractable material into contained fluent substances

ABSTRACT

A method of storing a fluent substance within a plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance.

BACKGROUND

A method of storing a fluent substance within a plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance.

Containers produced with high and low density polyethylene, polypropylene, polycarbonate, polyethylene terephthalate, polystyrene, polyvinyl chloride, or other plastics have been in use since about the early 1950's. In many instances, these plastic containers have replaced the use of glass containers for packaging products such as chemical salts, pesticides, foods, chemicals for production of semiconductors, pharmaceuticals, and a large array of consumer products. In addition, certain plastics are used to make containers for automobiles, such as fuel tanks.

There are various advantages of using plastic containers over glass containers and most other packaging materials. Plastic containers may be less costly to produce, easier to use as packaging, lower in weight, shipped at lower cost, and essentially non-breakable under normal conditions of use. As one non-limiting example, plastic bags as described in U.S. Pat. No. 6,729,369 to Neas et al. can be used to contain fluent substances.

Typically, there are two prominent considerations in choosing a suitable plastic material for a container; 1) the chemical and physical properties of these plastics in relationship to the properties of the chemical contents and 2) the cost of producing the container.

As to the first consideration, a substantial disadvantage of plastic containers can be that the walls of a plastic container can be permeable allowing passage of atmospheric gases and escape of the chemical contents, whether in the gaseous or liquid phase. Accordingly, as one non-limiting example, the plastic material used for production of fuel tanks can be selected to be fully impermeable to the contained fuel. Permeation to the outside of the plastic fuel tank could provide conditions leading to a fire or explosion.

For certain applications, plastic materials cannot be used with certain chemical contents. For example, glass containers are generally used to stably contain aqueous compositions intended for culturing microorganisms, animal cells, and human cells. This is because amino acids are readily oxidized and the glass bottle affords an oxygen barrier which plastic materials may not. Similarly glass containers can provide a carbon dioxide barrier in applications where a bicarbonate buffer system is used in growth media(s).

Another substantial disadvantage of plastic containers can be that the plastic reacts with or catalyzes a reaction of the chemical contents over the contents acceptable shelf life. For example, in food product applications it might be desirable to package products such as coffee or fruit juices in unbreakable, light weight or transparent plastic containers. However, plastic containers may absorb the essential oils and aroma components out of the food product. In the case of semiconductor applications, glass containers can be undesirable because ion contamination from the glass can contaminate the chemical contents. However, plastic containers exposed to chemicals used in semiconductor applications can stress crack.

Another substantial disadvantage of plastic containers can be extraction, leaching or transfer of compositions out of the plastic material which can affect the results of analytical testing methods. As one non-limiting example, most organic product analysis is done using high performance liquid chromatography and gas chromatography. It is estimated that there are approximately one half million of these analytical instruments in use worldwide. All of the millions of analytical methods performed by these instruments will use packaged organic chemicals as carriers in the testing method. Because such organic chemicals are capable of extracting materials from plastic materials such as high density polyethylene, high density polypropylene, or similar polymers almost all organic chemicals used in biochemical and analytical chemistry are packaged in glass containers, such as 4 liter bottles. A non-limiting example of an analytical method in which extractable material transferred from a plastic vessel to a fluent substance can interfere is HPLC chromatography as described below.

The pursuit of non-glass containers for transport of high purity solvents and organics that do not leach contaminants or reduce leaching of contaminants into the organics has led to containers made with fluorocarbon resins. As one non-limiting example, containers can be made with TEFLON® (perfluoroalkoxy vinyl ether). In addition, conventional high density polyethylene containers can be fitted with a TEFLON® bag or TEFLON® liner to protect the inside surfaces of these conventional plastic containers. However, such fluorocarbon plastic containers and conventional plastic containers fitted with a TEFLON® bag or liner can be extremely expensive which limits use. See for example, U.S. Pat. No. 4,948,641 to Shantz et al. and U.S. Pat. No. 4,871,087 to Johnson.

U.S. Pat. No. 5,770,135 to Hobbs et al. describes a process for producing polyethylene vessels treated with fluorine. The halogenated polyethylene vessel resists the outward migration of chlorobutanol from a solution through the vessel walls. Migration of chlorobutanol through the walls of polyethylene containers reduces the concentration of chlorobutanol in the solution stored within the polyethylene container. However, Hobbs does not disclose any assessment of the amount of extractable material transferred from the halogenated polyethylene vessels to the contents stored within the halogenated polyethylene vessel. Nor does Hobbs disclose a method of storing fluent substances within the halogenated polyethylene vessels to for the purpose of reducing the amount of extractable materials transferred from the plastic vessel to the fluent substance.

The instant invention provides a method for assessment of the materials extracted from plastic vessels into contained fluent substances and a method for the storage of fluent substance in plastic vessels which reduces extractable materials transferred to the contained fluent substances.

SUMMARY OF THE INVENTION

Accordingly, a broad object of the invention can be to provide a method of storing a fluent substance comprising containing a fluent substance within a plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from the plastic vessel to the contained fluent substance.

Another broad object of the invention can be to provide a method of plastic packaging of a fluent substance which reduces or substantially eliminates the transfer of extractable materials from the plastic material to the contained fluent substances.

Another broad object of the invention can be to provide a method of reducing extractable material in a fluent substance by containing the fluent substance in a plastic vessel prior contacted with a halogen containing gas under conditions to effect halogenation of the plastic material sufficient to reduce transfer of extractable material to the fluent substance.

Another broad object of the invention can be to provide a method of assessing the amount of extractable material transferred from a plastic container to the fluent substance stored within.

Naturally, further objects of the invention are disclosed throughout other areas of the specification, drawings, photographs, and claims.

A BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a conventional plastic material for a period of 24 hours at ambient temperature.

FIG. 2 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a conventional glass material for a period of 24 hours at ambient temperature.

FIG. 3 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a plastic container treated in accordance of the invention for a period of 24 hours at ambient temperature.

FIG. 4 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a conventional plastic material for a period of 14 days at ambient temperature.

FIG. 5 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a conventional glass material for a period of 14 days at ambient temperature.

FIG. 6 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a plastic container treated in accordance of the invention for a period of 14 days at ambient temperature.

FIG. 7 is a reverse phase gradient chromatograph of absorbance over time which evidences extractable materials produced by contact of a fluent substance with a conventional plastic material for a period of 14 days at ambient temperature and an additional 7 days at 60° C.

FIG. 8 is a first reverse phase gradient chromatograph (labeled F HDPE ACN) of absorbance over time which evidences extractable materials produced by contact of a fluent substance for a period of 14 days at ambient temperature and an additional 7 days at 60° C. with a treated plastic material made in accordance with a particular embodiment of the invention, and a second reverse phase gradient chromatograph (labeled Bottled ACN) of absorbance over time which evidences extractable materials produced by contact of a fluent substance for a period of 14 days at ambient temperature and an additional 7 days at 60° C. with a conventional glass material.

FIG. 9 is a reverse phase gradient chromatograph of absorbance over time which evidences an amount of extractable material produced by contact of acetonitrile with a HDPE for a time period of about one year vessel at ambient temperature.

FIG. 10 is a reverse phase gradient chromatograph of absorbance over time which evidences an amount of extractable material produced by contact of methanol with a HDPE vessel for a time period of about one year at ambient temperature.

FIG. 11 is a first reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences a lesser amount of extractable material produced by contact of acetonitrile with a glass vessel for a time period of about six months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of acetonitrile with a halogenated HDPE for a time period of about six months.

FIG. 12 is a first reverse phase gradient chromatograph of absorbance (215 nanometers) over time which evidences a lesser amount of extractable material produced by contact of acetonitrile with a glass vessel for a time period of about eight months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (215 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of acetonitrile with a halogenated HDPE for a time period of about eight months.

FIG. 13 is a first reverse phase gradient chromatograph of absorbance (235 nanometers) over time which evidences a lesser amount of extractable material produced by contact of acetonitrile with a glass vessel for a time period of about eight months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (235 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of acetonitrile with a halogenated HDPE for a time period of about eight months.

FIG. 14 is a first reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences a lesser amount of extractable material produced by contact of methanol with a glass vessel for a time period of about nine months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of methanol with a halogenated HDPE for a time period of about nine months.

FIG. 15 is a first reverse phase gradient chromatograph of absorbance (220 nanometers) over time which evidences a lesser amount of extractable material produced by contact of methanol with a glass vessel for a time period of about nine months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (220 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of methanol with a halogenated HDPE for a time period of about nine months.

FIG. 16 is a first reverse phase gradient chromatograph of absorbance (235 nanometers) over time which evidences a lesser amount of extractable material produced by contact of methanol with a glass vessel for a time period of about nine months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (235 nanometers) over time which evidences a similar lesser amount of extractable material produced by contact of methanol with a halogenated HDPE for a time period of about nine months.

FIG. 17 is a first reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences an amount of extractable material produced by contact of tetrahydrofuran with a glass vessel for a time period of about three months at ambient temperature and a second reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences an amount of extractable material produced by contact of tetrahydrofuran with a halogenated HDPE for a time period of about three months and third reverse phase gradient chromatograph of absorbance (254 nanometers) over time which evidences an amount of extractable material produced by tetrahydrofuran transferred from a first glass vessel to a second glass vessel.

FIG. 18 is an ultraviolet-visible spectrum of tetrahydrofuran.

FIG. 19 is an ultraviolet-visible spectrum of 2,6-di-t-butyl-p-cresol (“BHT”).

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A method of storing a fluent substance in a plastic vessel which reduces the amount of extractable material transferred from the plastic vessel to the fluent substance.

Now referring primarily to FIGS. 1-8, each of which provides a gradient chromatogram of absorbance against elapsed time during reverse phase gradient elution of extractable materials retained on a stationary phase of a chromatography column.

For the purposes of this invention the term “extractable material” means any substance, component, or chemical moiety transferred from a material upon contact by a fluent substance. For the purposes of this invention the terms “extracted”, “extraction” or “extracting” means chemical or mechanical action of a fluent substance on a material. The term “container” or “vessel” for the purposes of this invention means any configuration of a material capable of retaining a fluent substance such material can without limitation include a glass material or a plastic material. The term “glass material” has its usual meaning including without limitation glass containers and glass bottles. The term “plastic material” for the purpose of this invention means a thermoplastic such as high or low density polyethylene (HDPE, LDPE, PE), polypropylene (PP), polycarbonate (PC), polyethylene terephthalate (PET), polystyrene, polyvinyl chloride (PVC), butadiene (BD), polystyrene (PS), nylon (NY), or the like which has not been contacted with a halogen gas as described herein. The term “conventional plastic container” for the purposes of this invention means a plastic container which has not been halogenated or has not been assessed as being halogenated to an extent effective to reduce the amount of extractable material transferable to a contained fluent substance. The term “conventional HDPE container” for the purposes of this invention means an HDPE container which has not been halogenated or has not been assessed as being halogenated to an extent effective to reduce the amount of extractable material transferable to a contained fluent substance. The term “fluent substance” for the purposes of this invention means any liquid that can be contained by a container, including, as non-limiting examples: a biological fluid such as urine, blood, plasma, serum, or the like; organic solvents such as acetonitrile, methanol, ethanol, 2-propanol, tetrahydrofuran, acetone, cyclohexane, dichloromethane, chloroform, carbon tetrachloride, all aliphatic hydrocarbons greater or equal to 6 carbons as non-limiting examples hexane, heptane, octane, iso-octane, dimethylformamide, dimethyl sulfoxide, or the like; or aqueous solutions which contain salts or miscible organic solvents; or the like.

With respect to analytical chromatography, a chromatography column will typically provide a cylindrical flow path of between about one millimeter and about seven millimeters in diameter and a length of between about 50 millimeters and about 400 millimeters in length. The stationary phase for reverse phase chromatography (RPC) purposes will typically provide a population of substantially homogeneous sized particles of silica having a diameter of between about 3 μm and about 5 μm having a pore size of between about 80 Å and about 300 Å. The silica can be treated with RMe₂SiCl, where R is a straight chain alkyl group such as C₁₈H₃₇ or C₈H₁₇; although a variety of other straight chain alkyl groups or bifurcated alky groups can be utilized, which provide a ligand capable of providing retention of an analyte of interest, and specifically without limitation at least one extractable material as defined herein. One non-limiting example of chromatography column suitable for use in the analysis of extractable materials is a Waters Corporation, 300×3.9 mm, PN WAT 027324.

RPC operates on the principle of hydrophobic interactions, which result from repulsive forces between a polar eluent, a relatively non-polar analyte, and the non-polar stationary phase. The binding of the analyte to the stationary phase can be proportional to the contact surface area around the non-polar segment of the analyte molecule upon association with the ligand in the aqueous eluent. This solvophobic effect can be dominated by the partitioning of the analyte in the mobile phase and the C18-chain versus the complex of both. The analyte retention can be decreased by adding less-polar solvent (MeOH, ACN) into the mobile phase to reduce the hydrophobic interaction of the analyte with the stationary phase. Gradient elution uses this change in relative hydrophobicity by automatically changing the polarity of the mobile phase during the course of the analysis.

Structural properties of the analyte molecule play an important role in its retention characteristics. In general, an analyte with a greater hydrophobic nature (C—H, C—C, and generally non-polar atomic bonds, such as S—S and others) results in a longer retention time because it increases the molecule's partitioning into the non-polar stationary phase. On the other hand, polar groups, such as —OH, —NH₂, COO⁻ or —NH₃ ⁺ reduce retention as they are well integrated into water relative to the stationary phase. Large molecules, however, can result in an incomplete interaction between the large analyte surface and the ligands alkyl chains and can be restricted from entering the pores of the stationary phase.

Retention time increases with hydrophobic—non-polar—surface area. Branched chain compounds elute more rapidly than their corresponding linear isomers because the overall surface area is decreased. Similarly organic compounds with single C—C-bonds elute later than the ones with a C═C or C—C-triple bond, as the double or triple bond is shorter than a single C—C-bond.

Aside from mobile phase surface tension (organizational strength in eluent structure), other mobile phase modifiers can affect analyte retention. For example, the addition of inorganic salts causes a moderate linear increase in the surface tension of aqueous solutions (ca. 1.5 erg/cm² pro Mol for NaCl, 2.5 erg/cm² pro Mol for (NH₄)₂SO₄), and because the entropy of the analyte-solvent interface can be controlled by surface tension, the addition of salts tend to increase the retention time. This technique is used for mild separation and recovery of proteins and protection of their biological activity in protein analysis (hydrophobic interaction chromatography, HIC).

Another important component can be the influence of the pH since this can change the hydrophobicity of the analyte. For this reason most methods use a buffering agent, such as sodium phosphate, to control the pH. The use of buffers to control the pH of the mobile phase eluents and as a result, the analyte ionization. For example, the use of a more acidic buffer as an eluent prevents ionization of acidic compounds, thereby increasing hydrophobicity and partitioning into the non-polar stationary phase, causing better, but not necessarily greater, analyte retention. The effect varies depending on use but generally improve the chromatography.

The use of ion pairing reagents such as triethylamine (TEA) or sodium dodecylsulfate (SDS), when added to the eluent, enhances the analyte separation and partitioning into the stationary phase. In the case of TEA, the addition of this ion-pairing reagent deactivates the bare silica surface, resulting in an increase of analyte interaction with the stationary phase. This can be especially important for analytes that have a basic, rather than acidic, nature to them where the analyte would be attracted to the bare silica support. The addition of SDS adds another separation mechanism to the chromatographic system through the formation of micelles that surround a molecule that is ionic in nature. The ionic (hydrophilic) ends of the micelles are attracted to the analyte, while the hydrophobic tails of the micelle are left to partition into and out of the stationary phase.

It is not intended that the specific examples described herein of high performance liquid chromatography, chromatography columns, methods of reverse phase chromatography, and the plots or gradient chromatographs produced by utilization of reverse phase chromatography be limiting or preclude the analysis of extractable materials by other analytical means such as normal phase chromatography, size exclusion chromatography, ion exchange chromatography, mass spectrometry, gas chromatography whether used individually or in combination.

Additionally, for the purposes of the present invention, ranges may be expressed herein as from “about” one particular value to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. The term “about” will have the normal dictionary definition.

Moreover, for the purposes of the present invention, the term “a” or “an” entity refers to one or more of that entity; for example, “a plastic material” or “an extractable material” refers to one or more of those compounds or at least one compound. As such, the terms “a” or “an”, “one or more” and “at least one” can be used interchangeably herein. Furthermore, a material or compound “selected from the group consisting of” refers to one or more of the materials or compounds in the list that follows, including combinations of two or more of the materials or compounds.

Now referring to FIGS. 1-8 and Table 1. Table 1 sets out the stepwise application of an Eluent A (distilled water or water purified by reverse osmosis or application to molecular sieve) and an Eluent B (a fluent substance compatible for use as an eluent B for reverse phase chromatography such as acetonitrile stored for a period of time in a vessel whether glass or plastic and containing an amount of extractable material extracted from the vessel into the fluent substance) to a reverse phase chromatography column (Waters Corporation, Bondapak C18, 10μ particle, 300×3.9 mm, PN WAT 027324) at a flow rate of 2.0 milliliters per minute (“mL/min”)(“RP Column”). The chromatography column was cleaned of any extractable materials of prior samples by first eluting the RP Column with 100% Eluent B for a period of five minutes, extractable materials in Eluent B were then loaded on to the RP Column by applying Eluent A at 80% and Eluent B at 20% for 10 minutes, the extractable materials loaded on the RP Column were than eluted by application of a gradient of Eluent B from 20% to 100% over the subsequent 10 minute period. The RP Column was then equilabrated at 80% Eluent A to again load the RP Column with extractable material in Eluent B, the RP Column was then again eluted by application of a gradient of Eluent B from 20% to 100% over the subsequent 10 minute period. The gradient chromatographs of FIGS. 1-8 represent the absorbance of ultraviolet light at 254 nanometers by extractable materials in the eluent from the RP Column and background between 40 minutes and 85 minutes within the elution profile of Table 1. These analytical conditions are not intended to limiting with respect to the analysis of extractable materials utilizing other fluent substances as Eluent B, gradient schedules, analytical instrumentation or techniques, detection levels, absorption coefficients, or the like.

TABLE 1 Time (minutes) Eluent A (water) Eluent B (acetonitrile) 0 0 100 5 0 100 15 80 20 25 80 20 35 0 100 45 0 100 55 80 20 65 80 20 75 0 100 85 0 100

Now referring specifically to FIG. 1, which provides a gradient chromatogram of extractable material in an amount of acetonitrile. The acetonitrile containing extractable materials used as Eluent B was obtained by transferring an amount of acetonitrile to a conventional HDPE container and incubating the amount of acetonitrile in contact with a surface of the conventional HDPE container for a period of 24 hours (“hrs.”). As shown by the gradient chromatogram of FIG. 1 generated by using the above described chromatography method, the acetonitrile contained a plurality of extractable materials which eluted from the RP Column between about 72 minutes and about 79 minutes.

By comparison and now referring specifically to FIG. 2, a gradient chromatogram of extractable material in acetonitrile was obtained by the same procedure as described by the example of FIG. 1 except that the amount of acetonitrile was transferred to a conventional glass container and incubated in contact with the surface of the convention glass container for a period of 24 hrs. As shown by the gradient chromatogram of FIG. 2, no substantial amount of extractable material or a substantially reduced amount of extractable material by comparison to the chromatogram of FIG. 1, can be extracted by acetonitrile from a conventional glass container.

Now referring specifically to FIG. 3, which provides a gradient chromatograph of extractable material obtained by the same procedure as described by the examples of FIGS. 1 and 2 except that the amount of acetonitrile was transferred to an HDPE container substantially identical to that used in the example of FIG. 1, except that the HDPE container was contacted with a halogen gas under conditions to effect halogenation of the container wall (depending on the particular application halogenation can effect the entire thickness between surfaces of the container wall or a particular thickness of the container wall or the surface of the container wall) of the HDPE container sufficient to reduce the amount of extractable material extracted by contact with the acetonitrile (or other fluent substances contained within the plastic container). As evidenced by the gradient chromatogram of FIG. 3, the amount of extractable material extractable by acetonitrile in contact with a halogenated HDPE container can be reduced to a level comparable or even lower than the example of FIG. 2 of acetonitrile incubated in contact with a conventional glass container.

Contact of a plastic material such as an HDPE container (or other type of plastic container) with halogen gas under conditions to effect halogenation of the container surface or all or part of the thickness of the container wall of the HDPE container (or other plastic container) to reduce permeability of the plastic container to a particular fluent substance is not useful in determining the conditions to effect sufficient halogenation of the surface of the same HDPE container (or other type of plastic container) to substantially eliminate, or substantially reduce, or make comparable to glass (or other desired level depending upon the application) the amount extractable material transferable from an HDPE container (or other type of plastic container) to a fluent substance for the purpose of maintaining the purity of the fluent substance contained within the HDPE container (or other type of plastic container). Accordingly, the analytical chromatography methods described above along with the description, working examples and figures allows assessment of the amount, level, or degree of halogenation of a plastic material(s) effective to eliminate, substantially eliminate, or reduce the amount of extractable materials transferable to the fluent substance to the necessary, comparable or desired level. As non-limiting examples, reduction of the amount of extractable material in a stored fluent substance comparable to storage of the same fluent substance in a glass vessel over the same period of time.

As one non-limiting example, a halogen gas such as fluorine, chlorine, bromine, iodine can contact a plastic material in an amount of about 0.01 percent (“%”) to about 15% by volume in an inert gas such as argon, helium, nitrogen, or carbon dioxide. Typically, the halogen gas will comprise fluorine gas in an amount of about 0.05% to about 15% in carbon dioxide. The atmosphere about the plastic material can be purged and replaced with the inert gas or with hydrogen gas prior to contact with the halogen gas. The plastic material is typically treated above the self supporting temperate (the temperature above which the container will collapse if removed from the supporting mold) although the halogen containing gas contacting the plastic material can be at a lower temperature. Sufficient treatment of the plastic material with the halogen gas to reduce extractable materials can vary between plastic materials, the condition of the plastic material and can further vary depending upon the fluent substances to be contained by the plastic material. Accordingly, analysis for extractable material can be carried out as described herein or in similar fashion to determine the conditions sufficient to reduce, substantially eliminate, or achieve a certain level of extractable material in the context of a specific plastic material and a particular fluent substance.

With respect to the example of FIG. 3, the conventional HDPE container while at a temperature above self supporting and prior purged of atmosphere to provide a substantial absence of oxygen can be treated with fluorine gas at between about 0.5% and about 1.0% by volume in carbon dioxide for a duration of about one minute for purposes of reducing extractable material when contacted by acetonitrile. However, this is not intended to limit the treatment of an HDPE container solely to the above-described treatment but rather to a range of treatments which effect a reduction of extractable material to a desired level in the context of a contacting fluent substance and the duration of contact.

Now referring primarily to FIG. 4, which provides a gradient chromatogram generated using the chromatography conditions above described of an amount of extractable material in acetonitrile obtained by transferring an amount of acetonitrile to a conventional HDPE container and incubated in contact with a surface of the conventional HDPE container for a period of about fourteen days. As shown by the gradient chromatogram of FIG. 4, the plurality of extractable materials eluted between about 72 minutes and about 79 minutes substantially increases as compared to the extractable materials generated under similar or identical conditions during a 24 hr period.

Now referring primarily to FIG. 5, which provides a chromatogram of extractable material in an amount of acetonitrile obtained by the same procedure as described by the example of FIG. 4 except that the amount of acetonitrile was transferred to a conventional glass container and incubated in contact with the surface of the convention glass container for a period of about 14 days. As shown by the plot of the chromatogram of FIG. 5, and in comparison to the chromatogram of FIGS. 1 and 4, no substantial amount of extractable material or a substantially reduced amount of extractable material can be obtained from a conventional glass container.

Now referring primarily to FIG. 6, which provides a chromatograph of extractable material in an amount of acetonitrile obtained by the same procedure as described by the examples of FIGS. 4 and 5 except that the amount of acetonitrile was transferred to an HDPE container substantially identical to that used in the example of FIG. 1, with the HDPE container prior contacted with a halogen gas under conditions to effect halogenation of the HDPE container sufficient to reduce the amount of extractable material generated by contact with the acetonitrile. As evidenced by the gradient chromatogram of FIG. 6, the amount of extractable material generated by the halogenated HDPE container can be reduced to a level comparable or even lower than the example of FIG. 5 using a conventional glass container.

Now referring primarily to FIG. 7, which provides a gradient chromatogram of extractable material in acetonitrile obtained by transferring an amount of acetonitrile to a conventional HDPE container and incubated in contact with a surface of the conventional HDPE container for a period of fourteen days at ambient temperature and then incubated for 7 days at 60° centigrade (“C”). As shown by the plot of the chromatogram of FIG. 7, the plurality of extractable materials eluted between about 72 minutes and about 79 minutes substantially increases as compared to the extractable materials generated under similar or identical conditions during a 24 hr period or the 14 day period of FIGS. 1 and 4.

Now referring primarily to FIG. 8, which provides a first gradient chromatogram (labeled F HDPE ACN) of extractable material in acetonitrile obtained by transferring an amount of acetonitrile to an HDPE container conditioned with fluorine gas as above-described and a second gradient chromatogram (labeled GB ACN) of extractable material in acetonitrile obtained by transferring an amount of acetonitrile to a glass container, each then incubated in contact with a surface of the respective treated HDPE container or glass container for a period of fourteen days at ambient temperature and then incubated for 7 days at 60° centigrade (“C”). The first gradient chromatogram compared to the second gradient chromatogram evidences that the amount of extractable material in the acetonitrile incubated in the treated HDPE container was similar to that in the acetonitrile incubated in the conventional glass container.

The examples of FIGS. 1-8 demonstrate the affect of an organic solvent on plastic material containers in producing substantial amounts of extractable material which can increase with time and with increase in temperature. Accordingly, conventional plastic containers cannot be used to contain fluent substances later utilized in analytical, biochemical, pharmaceutical, and biological applications. However, the examples of FIGS. 1 through 8 above demonstrate there is no apparent difference in the amount of extractable material in contained fluent substances between glass containers and HDPE bottles conditioned by a level of halogenation of the plastic material in accordance with the invention. Each plastic container conditioned in accordance with the invention providing a container which does not generate, substantially eliminates or substantially reduces the amount of extracted material in comparison to conventional plastic containers, even under conditions of extended period of incubation with an aggressive organic solvent such as acetonitrile and even at elevated incubation temperatures of about 60° C.

Now referring to FIGS. 9-17, each of the gradient chromatograms was generated by equilibrating a reverse phase chromatography column (150 mm×4.6 mm Zorbax SB-C8 having a 5 micron particle size for the HPLC analysis of extractable materials in acetonitrile or a 150 mm×4.6 mm zorbax RX-C8 with a 5 micron particle size for HPLC analysis of extractable materials in methanol and tetrahydrofuran) as set out respectively in Table 2 and Table 3 using distilled water as eluent A and either acetonitrile, methanol or tetrahydrofuran (or other fluent substance being tested) containing an amount of extractable material as Eluent B. The flow rate during equilibration and elution was 1.5 mL/min. Acetonitrile, methanol, or tetrahydrofuran containing extractable materials were degassed by sparging with helium gas for at least 30 minutes prior to introduction to the respective reverse phase HPLC column.

The 150 mm×4.6 mm Zorbax SB-C8 having a 5 micron particle size for the HPLC analysis of extractable materials in acetonitrile was eluted using the gradient set out in Table 2. Acetonitrile (ACN) was monitored at 215 nm, 235 nm, and 254 nm. Methanol (MeOH) was monitored at 220, 235, and 254 nm. Tetrahydrofuran (THF) was monitored at 254 nm.

TABLE 2 Acetonitrile (wavelengths: 215/235/254) Time (minutes) Eluent % A (water) Eluent % B (Test Solvent) 0 70 30 20 0 100 25 0 100 30 70 30 35 70 30

The 150 mm×4.6 mm Zorbax RX-C8 with a 5 micron particle size for HPLC analysis of extractable materials in methanol and tetrahydrofuran was eluted using the gradient set out in Table 3. Methanol was monitored at 220, 235, and 254 nm, and Tetrahydrofuran was monitored at 254 nm.

TABLE 3 Methanol/THF (wavelengths: 220/235/254) Time (minutes) Eluent % A (water) Eluent % B (Test Solvent) 0 95 5 20 0 100 25 0 100 30 95 5 35 95 5

Now referring specifically to FIG. 9, which shows a reverse phase gradient chromatograph of absorbance over time obtained by eluting a 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored in a conventional HDPE vessel at ambient temperature for a time period of about one year. As can be understood from the reverse phase gradient chromatograms shown in FIG. 9 (as compared to the reverse phase gradient chromatograms shown in FIGS. 11 through 13 of the same lot of acetonitrile stored either in glass or in a HDPE vessel halogenated in accordance with the invention) a substantial amount of extractable materials can leach, extract or otherwise transfer from conventional HDPE vessels into the stored acetonitrile. The amount of extractable materials transferred to the acetonitrile stored in the conventional HDPE vessel can be assessed by retention of the amount of extractable material on a reverse phase chromatography column and subsequent elution using the gradient profile of Table 2 and monitored by ultraviolet detection at 254 nanometers. The detector sensitivity can be set at between zero and five hundred for assessment of fluent substances stored in conventional plastic vessels such as conventional non-halogenated HDPE vessels the gradient chromatograms otherwise being off scale.

Now referring specifically to FIG. 10, which shows a reverse phase gradient chromatograph of absorbance over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being methanol stored in a conventional HDPE vessel at ambient temperature for a time period of about one year. As can be understood from the reverse phase gradient chromatograms shown in FIG. 9 (as compared to the reverse phase gradient chromatograms shown in FIGS. 14 through 16 of the same lot of methonol stored either in glass or in a halogenated HDPE) a substantial amount of extractable materials can leach, extract or otherwise transfer from conventional HDPE vessels into the stored methanol. The amount of extractable materials transferred to the methanol stored in the conventional HDPE vessel can be assessed by retention on a reverse phase chromatography column and subsequent elution using the gradient profile of Table 3 and monitored by ultraviolet detection at 254 nanometers. The detector sensitivity set at between zero and five hundred for assessment of fluent substances stored in conventional plastic vessels such as conventional non-halogenated HDPE vessels the gradient chromatograms otherwise being off scale.

Now referring specifically to FIG. 11, which shows a first reverse phase gradient chromatograph (11A) of absorbance at 254 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored in a conventional glass vessel at ambient temperature for a time period of about six months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 11 (as compared to the reverse phase gradient chromatograms shown in FIGS. 9 of the same lot of acetonitrile stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored acetonitrile. The glass vessel being the industry standard to maintain fluent substances such as acetonitrile free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as acetonitrile are compared. FIG. 11 further provides a second reverse phase gradient chromatograph (11B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored for time period of about six months in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (11A) and the second reverse phase gradient chromatogram (11B) (separated vertically by 10 mAu for clarity) evidence that the amount of extractable materials within the acetonitrile stored in halogenated HDPE are substantially the same or less than the amount of extractable materials within the acetonitrile stored in conventional glass vessels.

Now referring specifically to FIG. 12, which shows a first reverse phase gradient chromatograph (12B) of absorbance at 215 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored in a conventional glass vessel at ambient temperature for a time period of about eight months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 12 (as compared to the reverse phase gradient chromatograms shown in FIGS. 9 of the same lot of acetonitrile stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored acetonitrile. The glass vessel being the industry standard to maintain fluent substances such as acetonitrile free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as acetonitrile are compared. FIG. 12 further provides a second reverse phase gradient chromatograph (12B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored for time period of about eight months in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (12A) and the second reverse phase gradient chromatogram (I 2B)(separated vertically by 10 mAu for clarity) evidence that the amount of extractable materials within the acetonitrile stored in halogenated HDPE are substantially the same or less than the amount of extractable materials within the acetonitrile stored in conventional glass vessels.

Now referring specifically to FIG. 13, which shows a first reverse phase gradient chromatograph (13A) of absorbance at 235 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with eluent B being acetonitrile stored in a conventional glass vessel at ambient temperature for a time period of about eight months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 13 (as compared to the reverse phase gradient chromatograms shown in FIGS. 9 of the same lot of acetonitrile stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored acetonitrile. The glass vessel being the industry standard to maintain fluent substances such as acetonitrile free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as acetonitrile are compared. FIG. 13 further provides a second reverse phase gradient chromatograph (13B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax SB-C8 in accordance with the stepwise gradient profile set out in Table 2 with Eluent B being acetonitrile stored for a time period of about eight months in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (13A) and the second reverse phase gradient chromatogram (13B) (separated vertically by 10 mAu for clarity) evidence that the amount of extractable materials within the acetonitrile stored in halogenated HDPE are substantially the same or less than the amount of extractable materials within the acetonitrile stored in conventional glass vessels.

Now referring specifically to FIG. 14, which shows a first reverse phase gradient chromatograph (14A) of absorbance at 254 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being methanol stored in a conventional glass vessel at ambient temperature for a time period of about nine months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 14 (as compared to the reverse phase gradient chromatograms shown in FIGS. 10 of the same lot of methanol stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored methanol. The glass vessel being the industry standard to maintain fluent substances such as methanol free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as methanol are compared. FIG. 14 further provides a second reverse phase gradient chromatograph (14B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with eluent B being methanol stored for time period of about nine months at ambient temperature in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (14A) and the second reverse phase gradient chromatogram (14B) (separated vertically by 10 mAu for clarity) evidence that the amount of extractable materials within the methanol stored in a HDPE vessel halogenated as above-described are substantially the same or less than the amount of extractable materials within the acetonitrile stored in conventional glass vessels.

Now referring specifically to FIG. 15, which shows a first reverse phase gradient chromatograph (15A) of absorbance at 220 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being methanol stored in a conventional glass vessel at ambient temperature for a time period of about nine months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 15 (as compared to the reverse phase gradient chromatograms shown in FIG. 10 of the same lot of methanol stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored methanol. The glass vessel being the industry standard to maintain fluent substances such as methanol free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as methanol are compared. FIG. 15 further provides a second reverse phase gradient chromatograph (15B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being methanol stored for time period of about nine months at ambient temperature in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (15A) and the second reverse phase gradient chromatogram (15B) (separated vertically by 500 mAu for clarity) evidence that the amount of extractable materials within the methanol stored in HDPE halogenated as above-described are substantially the same or less than the amount of extractable materials within the acetonitrile stored in conventional glass vessels.

Now referring specifically to FIG. 16, which shows a first reverse phase gradient chromatograph (16A) of absorbance at 235 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being methanol stored in a conventional glass vessel at ambient temperature for a time period of about nine months. As can be understood from the reverse phase gradient chromatograms shown in FIG. 16 (as compared to the reverse phase gradient chromatogram shown in FIG. 10 of the same lot of methanol stored in a conventional HDPE vessel) a substantially reduced amount of extractable materials leach, extract or otherwise transfer from glass vessels into the stored methanol. The glass vessel being the industry standard to maintain fluent substances such as methanol free of contaminants or extractable materials provides the standard by which results of the instant method of storing fluent substances such as methanol are compared. FIG. 16 further provides a second reverse phase gradient chromatograph (16B) of absorbance over time obtained by eluting the same 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with eluent B being methanol stored for time period of about nine months at ambient temperature in a HDPE vessel halogenated with fluorine as above-described. The first reverse phase gradient chromatogram (16A) and the second reverse phase gradient chromatogram (16B)(separated vertically by 10 mAu for clarity) evidence that the amount of extractable materials within the methanol stored in halogenated HDPE are substantially the same or less than the amount of extractable materials within the methanol stored in conventional glass vessels.

Now referring to FIG. 17, a first reverse phase gradient chromatograph (17A) of absorbance at 254 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being a control sample of stabilized tetrahydrofuran stored in the original packaging of a 4 L glass vessel at ambient temperature for a time period of about three months. The second reverse phase gradient chromatograph (17B) of absorbance at 254 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being a transfer control sample of stabilized tetrahydrofuran transferred from the original 4 L glass bottle to a second 4 L glass bottle as and stored at ambient temperature for a time period of about three months. The third reverse phase gradient chromatograph (17C) of absorbance at 254 nanometers over time obtained by eluting a 150 mm×4.6 mm Zorbax RX-C8 in accordance with the stepwise gradient profile set out in Table 3 with Eluent B being a first test sample of stabilized tetrahydrofuran transferred to a HDPE vessel halogenated with fluorine as above described. The gradient chromatograms 17A, 17B, and 17C are separated by 100 mAu for clarity purposes and the separation of these gradient chromatograms in this manner is not on account of any additional background in the samples analyzed.

As can be understood by a comparison of the reverse phase gradient chromatograms shown in FIG. 17 of the control samples (17A and 17B) and the first test sample of stabilized tetrahydrofuran (17C) there is substantially no difference in the amount of extractable materials or oxygen generated peroxides. Therefore, there is no apparent difference between the method of storing stabilized tetrahydrofuran in glass vessels such as the conventional packaging of stabilized tetrahydrofuran in a 4 L bottle and the instant method of storing stabilized tetrahydrofuran in a HDPE bottle halogenated as above-described (and in particular halogenated with fluorine as above-described).

Now referring specifically to FIGS. 18 and FIG. 19 and Table 4. Non-stabilized tetrahydrofuran is an ether which when exposed to oxygen (whether atmospheric oxygen or otherwise) can generate peroxides of tetrahydrofuran. The peroxides formed upon exposure to oxygen can be substantially eliminated or reduced by the addition of butylated hydroxytoluene (“BHT”). However, addition of BHT to tetrahydrofuran can interfere with the ultraviolet-visible transparency of the tetrahydrofuran at certain wavelengths. See FIG. 19 which provides a UV spectrum of BHT. Thus for many applications a non-stabilized tetrahydrofuran must be utilized. See FIG. 18 which provides a UV spectrum of non-stabilized tetrahydrofuran.

Accordingly, a method of storing non-stabilized tetrahydrofuran must first substantially eliminate migration or transfer of oxygen to the stored non-stabilized tetrahydrofuran whether migration of oxygen into the non-stabilized tetrahydrofuran occurs through the walls of the vessel in which the non-stabilized tetrahydrofuran is stored or between the engaged surfaces of the vessel closure. Second, the method of storing non-stabilized tetrahydrofuran must substantially eliminate extractable materials from being leached, extracted, or otherwise transferred from the storage vessel into the stored non-stablized tetrahydrofuran.

Two aliquots of non-stabilized tetrahydrofuran were transferred from a conventional glass vessel comprising the original packaging of a non-stabilized tetrahydrofuran one to each of two HDPE vessels halogenated as above-described. One of the two halogenated HDPE vessels was further placed inside an envelop containing an inert gas to control for migration of atmosphere through the vessel walls of the halogenated HDPE vessel. As a control to replicate any consequence of the transfer, a similar aliquot of non-stabilized tetrahydrofuran was transferred from a conventional glass bottle to another conventional glass bottle. The transferred aliquots of non-stabilized tetrahydrofuran were then blanketed with an inert gas such as nitrogen and the vessels sealed with the corresponding vessel closures.

The resulting four samples of non-stabilized tetrahydrofuran comprising the control sample (non-stabilized tetrahydrofuran in the original packaging comprising a 4 liter glass vessel)(“CTRL”), a transfer control sample (non-stabilized tetrahydrofuran transferred from the original packaging of a 4 liter glass bottle to a second substantially identical 4 liter glass bottle)(“GT”), a first test sample (non-stabilized tetrahydrofuran transferred from the original packaging comprising a 4 liter glass bottle to a HDPE vessel halogenated as above-described sealed with a nitrogen atmosphere in the head space)(“FDHPE”) and a second test sample (non-stabilized tetrahydrofuran transferred from the original packaging comprising a 4 liter glass bottle to a HDPE vessel halogenated as above-described sealed with a nitrogen atmosphere in the head space and further placed in an envelope containing an atmosphere of inert gas)(“FDHPEO”) were stored for a time period of about three months at ambient temperature.

Subsequently, two hundred and fifty milliliters (“mL”) of each of the four samples of non-stabilized tetrahydrofuran comprising the above-described CTRL, GT, FDHPE and FDHPEO samples were obtained by breaching the respective vessels, transferring an aliquot of 250 mL for analysis and resealing the respective sample vessels after re-establishing an inert atmosphere in the head space. Fifty milliliters of each of the four samples were analyzed by ultraviolet (“UV”) scan between 332 nanometers and 365 nanometers with a Beckman DU-520 Spectrophotometer. The absorbance values for each of the four samples (CTRL, GT, FDHPE and FDHPEO) of non-stabilized tetrahydrofuran are set out in Table 4 below along with water (HOH) as an instrument control.

TABLE 4 Ultraviolet Scan of Samples Of Unstabilized Tetrahydrofuran SAMPLE Absorbance at nm in AU Wavelength, nm CTRL GT FDHPE FDHPEO HOH 365 0.034 0.035 0.036 0.032 0.037 361 0.034 0.036 0.037 0.033 0.037 359 0.035 0.036 0.037 0.033 0.038 358 0.034 0.035 0.038 0.034 0.038 354 0.034 0.035 0.037 0.033 0.037 353 0.035 0.036 0.038 0.033 0.038 352 0.035 0.036 0.039 0.033 0.038 348 0.035 0.036 0.039 0.034 0.038 344 0.035 0.036 0.04 0.034 0.038 339 0.035 0.037 0.043 0.034 0.039 333 0.036 0.037 0.046 0.035 0.039 332 0.036 0.037 0.047 0.035 0.039

The absorbance value data for the four samples of non-stabilized tetrahydrofuran demonstrates that there was virtually no difference in the UV absorbance between the controls (“CTRL” and “GT”) and the rest of the FDHPE and FDHPEO test samples stored in accordance with the inventive method. Therefore, there is no apparent difference between non-stabilized tetrahydrofuran stored by the conventional method in a glass vessel (“CTRL”) and the FDHPE and FDHPEO samples stored in a halogenated plastic vessel in accordance with the inventive method and specifically as to the results of Table 4 in a HDPE vessel halogenated with fluorine as above described.

Now referring primarily to Table 5. A 200 mL aliquot of each the four samples CTRL, GT, FDHPE and FDHPEO were evaporated to dryness in a corresponding tared weighing dish. The heat source used in the evaporation step was a hot plate set at about 150 centigrade (“° C.”). Upon evaporation of the respective aliquots, the dish was removed from the hot plate, placed in a dessicator, and allowed to cool to room temperature. The cooled dished was reweighed and the weight of the residue calculated. The weighing dish used in this procedure was a 70 mm diameter aluminum dish that features a finger-grip handle on the rim. The dish had a liquid volume of 50 mL. The volume of each dish was re-filled after dryness until all 200 mL of each of the corresponding four samples had been consumed. The weight of the residue in each dish upon evaporation was calculated out to four decimal places by subtracting the recorded tare weight of each of the four dishes from the corresponding recorded gross weight of each dish to establish the net weight of the residue in each dish. The residue in milligrams per milliliter of each of the four samples was calculated.

TABLE 5 Residue From Samples Of Unstabilized Tetrahydrofuran. Wt. of Aluminum SAMPLE Pan CTRL GT FDHPE FDHPEO Gross, mg 1019.82 1005.90 1016.50 997.60 Tare, mg 1019.69 1005.97 1016.24 997.53 Net, mg 0.13 −0.07 0.26 0.07 Aliquot, mL 200 200 200 200 Residue (mg/mL) 0.0006 −0.0004 0.0013 0.0004 mg/L 0.65 −0.35 1.30 0.35

The data in Table 5 demonstrates that there is virtually no difference in the residue amounts between the control (CTRL) transfer control (GT) and the test samples (FDHPE and FDHPEO). Therefore, there is no apparent difference between conventional method of storing non-stabilized tetrahydrofuran in glass vessels and the inventive method of storing fluent substances such as non-stabilized tetrahydrofuran in a plastic container halogenated as above-described.

Now referring specifically to Tables 6 and 7. The fluent substances above described are each water soluble and useful in analytical methods such as HPLC and similar analytical methods. Accordingly, the inventive storage method was assessed for non-water soluble fluent substance such as the non-polar solvent hexane which is often used in gas chromatography and similar analytical methods. The above described UV visible spectrometry and residue analysis procedures were used to assess of the utility of the inventive method for storage of hexane. A hexane control sample (“HCTRL”) was obtained by storing hexane in the original packaging comprising a 4 L glass vessel for 3 months at ambient temperature and the a test sample of hexane was obtained by storing hexane in a HDPE vessel halogenated as above-described for three months at ambient temperature and specifically with respect to the data shown in Table 6, the HDPE vessel was halogenated with fluorine as above-described.

TABLE 6 Ultraviolet Scan of Hexane Samples. SAMPLE Absorbance at nm in AU Wavelength, nm HCTRL HFDHPE HOH 390 0.039 0.034 0.037 370 0.041 0.034 0.038 350 0.042 0.035 0.038 330 0.044 0.036 0.040 310 0.047 0.037 0.041 290 0.055 0.039 0.044 275 0.059 0.041 0.046 270 0.059 0.042 0.047 260 0.061 0.044 0.048 240 0.077 0.056 0.054 220 0.151 0.116 0.070 215 0.203 0.161 0.077 210 0.313 0.249 0.089 205 0.461 0.388 0.106 200 0.629 0.571 0.132 190 1.073 1.064 0.356

The absorbance value data for the hexane control sample (HCTRL) and the hexane test samples (HFDHPE) demonstrates that there was virtually no difference in the UV absorbance. Therefore, there is no apparent difference between method of storing hexane by the conventional method in a glass vessel and the inventive method of storing hexane n a halogenated plastic vessel and specifically as to the data of Table 6 in a HDPE vessel halogenated with fluorine, as above described.

TABLE 7 Residue From Hexane Samples. Wt. of Aluminum SAMPLE Pan CTRL FDHPE Gross, mg 1633.92 1646.24 Tare, mg 1633.95 1646.23 Net, mg −0.03 0.01 Aliquot, mL 200 200 Residue (mg/mL) −0.0001 0.0000 mg/L −0.15 0.05

The data in Table 7 demonstrates that there is virtually no difference in the residue amounts between the hexane control sample (HCTRL) the hexane samples. Therefore, there is no apparent difference between conventional method of storing hexane in glass vessels and the inventive method of storing fluent substances such as hexane in a plastic container halogenated as above-described.

A plastic material configured to contain a fluent substance having been sufficiently halogenated to effect reduction in at least one extractable material upon contact with the fluent substance provides various advantages over conventional glass containers and conventional plastic containers.

First, glass containers and conventional fluoropolymer containers are expensive relative to plastic materials treated in accordance with the invention to reduce production of extractable materials. Additionally, glass containers weigh more than the comparable plastic container treated in accordance with the invention. Accordingly, the cost to ship conventional glass containers can be greater than the corresponding inventive container. Moreover, conventional glass containers can readily break while the inventive container is substantially less prone to breakage.

Second, plastic materials configured to contain a fluent substance treated in accordance with the invention to reduce extractable materials in contained fluent substances can be used for dispensing pre-prepared mixed reagents, high purity solvents, sanitizers, disinfectants, or the like in which extractable materials may not be acceptable in the context of the application such as compositions: delivered to animals or humans as injectables; used in end-product fabrication or quality control testing in the biochemical and analytical applications; in-line monitoring or mixing constituents of a product; sample bench testing of end-products or constituents thereof for purposes of quality control; bench-testing of a product undergoing research or to assess its manufacturability; material identification, measuring properties and behavior, or the like. In general, the inventive method and apparatus can be used anywhere in which extractable material from a plastic material in a fluent substance would be a concern.

Third, use of the inventive plastic materials to contain a fluent substance increases safety in that the treated plastic materials configured to contain a fluent substance are essentially unbreakable. This reduces the risk of contact between the contained fluent substance and animals or humans.

As can be easily understood from the foregoing, the basic concepts of the present invention may be embodied in a variety of ways. The invention involves numerous and varied embodiments of a plastic packaging system for the reduction of extractable materials by a contained fluent substance and methods of plastic packaging a fluent substance to reduce extractable materials.

As such, the particular embodiments or elements of the invention disclosed by the description or shown in the figures or tables accompanying this application are not intended to be limiting, but rather exemplary of the numerous and varied embodiments generically encompassed by the invention or equivalents encompassed with respect to any particular element thereof. In addition, the specific description of a single embodiment or element of the invention may not explicitly describe all embodiments or elements possible; many alternatives are implicitly disclosed by the description and figures.

It should be understood that each element of an apparatus or each step of a method may be described by an apparatus term or method term. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled. As but one example, it should be understood that all steps of a method may be disclosed as an action, a means for taking that action, or as an element which causes that action. Similarly, each element of an apparatus may be disclosed as the physical element or the action which that physical element facilitates. As but one example, the disclosure of “a reduced amount of extractable material” should be understood to encompass disclosure of the act of “reducing an amount of extractable material”—whether explicitly discussed or not—and, conversely, were there effectively disclosure of the act of “reducing an amount of extractable material”, such a disclosure should be understood to encompass disclosure of “a reduced amount of extractable material” and even a “means for reducing an amount of extractable material.” Such alternative terms for each element or step are to be understood to be explicitly included in the description.

In addition, as to each term used it should be understood that unless its utilization in this application is inconsistent with such interpretation, common dictionary definitions should be understood to included in the description for each term as contained in the Random House Webster's Unabridged Dictionary, second edition, each definition hereby incorporated by reference.

Thus, the applicant(s) should be understood to claim at least: i) each of the plastic packaging systems herein disclosed and described, ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these devices and methods, iv) those alternative embodiments which accomplish each of the functions shown, disclosed, or described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, ix) methods and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, x) the various combinations and permutations of each of the previous elements disclosed.

The background section of this patent application provides a statement of the field of endeavor to which the invention pertains. This section may also incorporate or contain paraphrasing of certain United States patents, patent applications, publications, or subject matter of the claimed invention useful in relating information, problems, or concerns about the state of technology to which the invention is drawn toward. It is not intended that any United States patent, patent application, publication, statement or other information cited or incorporated herein be interpreted, construed or deemed to be admitted as prior art with respect to the invention.

The claims set forth in this specification, if any, are hereby incorporated by reference as part of this description of the invention, and the applicant expressly reserves the right to use all of or a portion of such incorporated content of such claims as additional description to support any of or all of the claims or any element or component thereof, and the applicant further expressly reserves the right to move any portion of or all of the incorporated content of such claims or any element or component thereof from the description into the claims or vice-versa as necessary to define the matter for which protection is sought by this application or by any subsequent application or continuation, division, or continuation-in-part application thereof, or to obtain any benefit of, reduction in fees pursuant to, or to comply with the patent laws, rules, or regulations of any country or treaty, and such content incorporated by reference shall survive during the entire pendency of this application including any subsequent continuation, division, or continuation-in-part application thereof or any reissue or extension thereon.

The claims set forth in this specification, if any, are further intended to describe the metes and bounds of a limited number of the preferred embodiments of the invention and are not to be construed as the broadest embodiment of the invention or a complete listing of embodiments of the invention that may be claimed. The applicant does not waive any right to develop further claims based upon the description set forth above as a part of any continuation, division, or continuation-in-part, or similar application. 

1. A method of storing a fluent substance, comprising the step of: containing a fluent substance within a plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance.
 2. The method of storing a fluent substance as described in claim 1, further comprising the step of assessing said amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance.
 3. The method of storing a fluent substance as described in claim 2, further comprising the step of adjusting extent of halogenation of said plastic vessel effective to reduce said amount of extractable material transferred from said plastic vessel to said fluent substance to a pre-determined amount of said at least one extractable material transferred from said plastic vessel to said fluent substance.
 4. The method of storing a fluent substance as described in claim 3, further comprising the step of reducing said amount of extractable material in said fluent substance contained within said plastic vessel to an amount substantially comparable to said fluent substance contained in a glass vessel.
 5. The method of storing a fluent substance as described in claim 4, wherein said plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance comprises a plastic vessel having a halogenated plastic material selected from the group consisting of: a high density polyethylene, a low density polyethylene, a polyethylene, a polypropylene, a polycarbonate, a polyethylene terephthalate, a polystyrene, a polyvinyl chloride, a butadiene, and a nylon.
 6. The method of storing a fluent substance as described in claim 4, wherein said plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance is halogenated by contact with a halogen gas selected from the group consisting of: fluorine, chlorine, bromine, and iodine.
 7. The method of storing a fluent substance as described in claim 4, wherein said plastic vessel halogenated to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance comprises a plastic vessel of high density polyethylene halogenated with a fluorine gas at temperature above self supporting to an extent effective to reduce an amount of at least one extractable material transferred from said plastic vessel to said contained fluent substance.
 8. The method of storing a fluent substance as described in claim 7, wherein said fluorine gas has a concentration of between about 0.01 percent by volume and about 15 percent by volume in an inert gas.
 9. The method of storing a fluent substance as described in claim 8, wherein said inert gas is selected from the group consisting of argon, helium, nitrogen, or carbon dioxide.
 10. The method of storing a fluent substance as described in claim 9, further comprising the step of contacting said plastic vessel of high density polyethylene with said fluorine gas at temperature above self supporting for a period of time in the range of about fifteen seconds to about 120 seconds.
 11. The method of storing a fluent substance as described in claim 5, wherein said halogenated plastic material is generated by contacting said plastic vessel at temperature above self supporting with fluorine gas having a concentration in the range of about 0.5 percent by volume and about 1.0 percent by volume in carbon dioxide for a duration of time in the range of about fifteen seconds to about 120 seconds.
 12. The method of storing a fluent substance as described in claim 1, wherein said fluent substance is selected from the group consisting of: an amount of a biological fluid, an amount of urine, an amount of blood, an amount of plasma, an amount of serum, an amount of an organic solvent, an amount of alcohol, an amount of acetonitrile, an amount of dichloromethane, an amount of dimethylformamide, and an amount of an aqueous solution.
 13. The method of storing a fluent substance as described in claim 2, wherein said fluent substance is selected from the group consisting of: an amount of a biological fluid, an amount of urine, an amount of blood, an amount of plasma, an amount of serum, an amount of an organic solvent, an amount of alcohol, an amount of acetonitrile, an amount of dichloromethane, an amount of dimethylformamide, and an amount of an aqueous solution.
 14. The method of storing a fluent substance as described in claim 3, wherein said fluent substance is selected from the group consisting of: an amount of a biological fluid, an amount of urine, an amount of blood, an amount of plasma, an amount of serum, an amount of an organic solvent, an amount of alcohol, an amount of acetonitrile, an amount of dichloromethane, an amount of dimethylformamide, and an amount of an aqueous solution.
 15. The method of storing a fluent substance as described in claim 4, wherein said fluent substance is selected from the group consisting of: an amount of a biological fluid, an amount of urine, an amount of blood, an amount of plasma, an amount of serum, an amount of an organic solvent, an amount of alcohol, an amount of acetonitrile, an amount of dichloromethane, an amount of dimethylformamide, and an amount of an aqueous solution.
 16. The method of storing a fluent substance as described in claim 7, wherein said fluent substance is selected from the group consisting of: an amount of a biological fluid, an amount of urine, an amount of blood, an amount of plasma, an amount of serum, an amount of an organic solvent, an amount of alcohol, an amount of acetonitrile, an amount of dichloromethane, an amount of dimethylformamide, and an amount of an aqueous solution. 17-19. (canceled) 